1. ABSTRACT: For decades, public health officials have been concerned about the reoccurrence of pandemic influenza. The worst documented pandemic occurred in 1918-1919, killing an estimated 20-40 million people worldwide. Although influenza has not wreaked such havoc since then, there have been close calls -- most recently with the avian influenza strain currently circulating in SE Asian poultry flocks. In the meantime, new threats have emerged. SARS has been the most widespread of these, and has carried a high human and economic toll where it has struck. Will one of these new diseases take the place of the dreaded influenza?

2. The New Flu? Pandemic Influenza, Avian Flu, and SARS Amy D. Sullivan, Ph.D, MPH Epidemiologist Multnomah County Health Department

3. ThenNow

4. Topics for This Evening… Review the Pandemic Flu of 1918- 1919 Was it really that bad? (Hint: Yes) How could it have happened? Subsequent threats Avian flu SARS Discuss: Is another event like pandemic flu inevitable?

6. What Was So Striking… Characteristic symptoms & outcomes High global death tolls Large numbers of deaths among healthy adults So completely ignored for so long

7. Characteristic Symptoms and Outcomes “…dusky heliotrope cyanosis of the face, lips, and ears… [and] purulent bronchitis with bronchopneumonia” (Oxford, 2001) Case fatality proportion 25-50%

8. The Death Toll Global estimates 1920’s: ~21.5 million dead India alone: 18 million 1998 conference: 50-100 million Varied greatly by country & region Europe & N. America: 3-20 deaths/1,000 Africa: 20-445 deaths/1,000 people Asia/Pacific: 3-220 deaths/1,000 people

9. Oct-Nov 1918 (second wave)

10. Deaths Among Healthy Adults Influenza deaths usually among youngest & oldest Rates during 1918 Infants & over 40 ~2-10-fold higher 10-20 yrs old: 20-100-fold higher 20-30 yrs old 20-180-fold higher

11. Multnomah County Deaths (3 month period; Total deaths ~20,200)

12. Was Pandemic Flu Really That Bad? Yes… In thinking about the potential of Avian flu (or other emerging respiratory illnesses) to wreak havoc, useful to understand…

13. How Could Such a Catastrophic Event Occur? Biologic factors Segmented genome of the influenza virus Unique to influenza viruses? Epidemiologic Factors Route of transmission Population movements/migrations “Seeding” the population

14. The Influenza A Virus Typically spherical 50-120 nm diameter Single-stranded RNA virus Genome in 8 segments Encode key surface glycoproteins Haemagglutinin (HA) Neuraminidase (NA)

15. The Segmented Genome At Work Genome segments can exist inside host cell “naked & free” Role of HA in cell infection

16. Flu Haemaglutinin 15 subtypes identified allow for… Variability in human infection H1, H2, & H3 pandemic potential H5 poor human-human spread H7 birds not humans Different possible host species H1: birds, pigs, & people H5: birds & people

17. Shift vs. Drift Influenza viruses change regularly Usually “antigenic drift” “Normal” mutations Changes in surface glycoprotiens but can cross-react with existing immunity Sometimes “antigenic shift” Segments can rearrange when co- infecting same cell  Reassortments by very different strains can profoundly change ability to recognize

18. “Spanish Flu” & Antigenic Shift H1N1 subtype of Influenza A H1 from an antigenic shift Avian origin? Avian via swine? Poor population-level immunity key in devastation Virulence factors not ruled out

19. Influenza Virulence Infects respiratory tract epithelial cells Ciliated & serous; not basal Upper respiratory infection less severe then infection in lungs Mutation(s) affecting speed or invasiveness of infection? Affect mortality And transmission?

20. Infection & Transmission 15-60% of infected people develop symptoms Incubation period: 1-3 days Infectious period: 3-7 days after symptom onset Symptomatic most likely to transmit Mode of transmission: Fomite possible Droplet or aerosol

21. Droplet vs. Aerosolized Spread Droplet transmission Respiratory secretions >5  m Fall out of air quickly with ~3 feet Easier to protect against? Aerosolized transmission Respiratory secretions <5  m Can stay airborne for hours Both can occur for any one disease

22. Population Mixing an the Spread of Spanish Flu 1918-19 a time of great social upheaval 1914: Great Britain declares war on Germany 1917: U.S. joins WWI 1918: U.S. troops arriving in Europe; Armistice signed at end of year 1919: Armies head home Airplanes not a factor, but huge movements of people in the world

23. “Seeding” the Population First appearance in 1918? First described in Fort Riley, Kansas in March 1918 “…near simultaneous appearance [of flu] in March-April 1918 in North America, Europe, and Asia…” (Taubenberger, 2001) Pandemic flu strain likely existed before 1918 (but not for long)

24. Etaples, France. 1916 WWI British Army base Crowded conditions: animals & people People from all over the Empire Outbreak of “Purulent Bronchitis” Dec 1916 thru spring 1917 Case fatality ~45% Bacillus influenza (a.k.a. Haemophilis influenza) in 18 of 20 cases Earliest documented report

25. How Could Such a Catastrophic Event Occur? Biologic factors High infectivity with novel “look” (immunologically)  Analogous to zoonotic disease but better adapted Epidemiologic Factors Droplet & aerosolized transmission Occurred at a time of global migration Was able to “seed” itself around the globe

26. Avian Influenza H5N1 Hong Kong, 1997 18 people hospitalized; 6 die Hundreds likely ill Young adults affected Infection directly from chickens Most avian flu viruses do not directly infect humans No person-to-person transmission

27. Avian Flu in 2003-4 December 2003 H5N1 avian flu identified in Vietnam By March 10 th, 2004 33 cases with 22 deaths in Vietnam and Thailand Infected birds in 8 Asian countries  Cambodia, China, Indonesia, Japan, Laos, South Korea, Thailand, and Vietnam Investigation of person-person transmission in Vietnam case

28. Could a Catastrophic Event Occur? Biologic factors High infectivity with novel “look” (immunologically) Epidemiologic Factors Droplet & aerosolized transmission – Rare for person-to-person Occurred at a time of global migration Was able to “seed” itself around the globe - NO

29. Severe Acute Respiratory Syndrome (SARS) Pneumonia caused by a coronavirus Fatal pneumonia Fever (>100.4 F or 38 C); Dry cough, shortness of breath, difficulty breathing Tx: Supportive therapy only Incubation period, ~6 days Case fatality proportion, 5-15% Much higher in persons over 60 years

30. Discovering SARS First recognized in Viet Nam, February 2003 Businessman traveled from Guangdong Hospital outbreak among persons exposed to him Occurred in Guangdong Province as early as November 2002

31. Where Is SARS From Don’t know for sure In Guangdong Province market Identified in exotic animals sold for food Seropositive asymptomatic individuals among sellers Circulating before this outbreak?

32. How is SARS Spread? Droplet? Close contact appears important  Household contacts  Healthcare workers But… many unanswered questions Aerosol pattern in some cases “Superspreaders” Still unsure about…  Fomite transmission  Asymptomatic transmission

33. Amoy Gardens, Hong Kong Aerosolized virus from improperly ventilated U- traps spread up outside ventilation shaft in an apartment building

34.                                SARS Cases Reported to WHO as of June 13, 2003 8,445 cases; 790 deaths

35. Current SARS Situation Chinese outbreak from apparent infection in a research lab 8 cases (confirmed and suspected)  All cases epidemiologically linked ~1,000 contacts under surveillance  640 in Beijing; 353 in Anhui Provence  Virology Institute closed

36. Could a Catastrophic Event Occur? Biologic factors High infectivity with novel “look” (immunologically) Epidemiologic Factors Droplet & aerosolized transmission – Rare for person-to-person Occurred at a time of global migration Was able to “seed” itself around the globe - NO

37. Discuss Is another event like pandemic flu inevitable?